Investigation of mutations in hotspot regions of ERG11 gene in fluconazole-resistant isolates of Candida albicans in the west of Mazandaran

Subject Areas : Molecular Microbiology

Masoumeh  Majdi ¹ (دانشجوی کارشناسی ارشد، گروه زیست شناسی سلولی و مولکولی، دانشکده علوم زیستی، واحد تنکابن، دانشگاه آزاد اسلامی، تنکابن)
Zeinab  Khazaei Koohpar ² (استادیار، گروه زیست شناسی سلولی و مولکولی، دانشکده علوم زیستی، واحد تنکابن، دانشگاه آزاد اسلامی، تنکابن)
Ayatallah  Nasrolahi Omran ³ (دانشیار، گروه قارچ شناسی پزشکی، واحد تنکابن، دانشگاه آزاد اسلامی، تنکابن)

Received: 2017-12-03 Accepted : 2018-01-23 Published : 2018-11-22

Keywords: Candida albicans, Fluconazole, ERG11, V488I mutation, D504V mutation,

Abstract :

Background & Objectives: Nowadays, widespread use of fluconazole has resulted in resistance in Candida albicans strains. The conformational changes of Erg11p due to mutations in the ERG11 gene is one of the mechanisms resulting in azole resistance. The aim of our study was to investigate ERG11 gene mutations in fluconazole-resistant isolates of C. albicans in the west of Mazandaran province.Materials & Methods: In this descriptive cross-sectional study, clinical specimens were obtained from vaginal mucosa of 120 women in hospitals of the west of Mazandaran province. C. albicans isolates were identified by standard methods such as germ tubes and CHROMEagar medium culture. The fluconazole resistance and susceptibility of the isolates were evaluated by Kirby Bauer and broth micro-dilution methods. Then, ERG11 gene mutations in resistant isolates were determined by PCR-sequencing method as compared with PTCC5027 (ATCC10231) reference strain.Results: Out of 45 C. albicans isolates, 40 isolates were resistant and 5 isolates were susceptible to fluconazole. The MIC of fluconazole was determined as ≥ 64 µg/ml. PCR-sequencing analysis revealed that 18 fluconazole-resistant isolates have six missense mutations (Y257H, E266D, V404I, D421N, V488I, and D504V) in the ERG11 gene.Conclusion: The identified mutations in this study may play role in developing fluconazole resistance in C. albicans isolates in the west of Mazandaran province by decreasing fluconazole affinity to ERG11p.

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